ID GLHA_HUMAN Reviewed; 116 AA. AC P01215; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 13-FEB-2019, entry version 196. DE RecName: Full=Glycoprotein hormones alpha chain; DE AltName: Full=Anterior pituitary glycoprotein hormones common subunit alpha; DE AltName: Full=Choriogonadotropin alpha chain; DE AltName: Full=Chorionic gonadotrophin subunit alpha; DE Short=CG-alpha; DE AltName: Full=Follicle-stimulating hormone alpha chain; DE Short=FSH-alpha; DE AltName: Full=Follitropin alpha chain; DE AltName: Full=Luteinizing hormone alpha chain; DE Short=LSH-alpha; DE AltName: Full=Lutropin alpha chain; DE AltName: Full=Thyroid-stimulating hormone alpha chain; DE Short=TSH-alpha; DE AltName: Full=Thyrotropin alpha chain; DE Flags: Precursor; GN Name=CGA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=481597; DOI=10.1038/281351a0; RA Fiddes J.C., Goodman H.M.; RT "Isolation, cloning and sequence analysis of the cDNA for the alpha- RT subunit of human chorionic gonadotropin."; RL Nature 281:351-356(1979). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8196184; RA Miyoshi I., Kasai N., Hayashizaki Y.; RT "Structure and regulation of human thyroid-stimulating hormone (TSH) RT gene."; RL Nippon Rinsho 52:940-947(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98. RX PubMed=6286817; RA Fiddes J.C., Goodman H.M.; RT "The gene encoding the common alpha subunit of the four human RT glycoprotein hormones."; RL J. Mol. Appl. Genet. 1:3-18(1981). RN [5] RP PROTEIN SEQUENCE OF 1-24 (PRECURSOR PROTEIN). RX PubMed=7462224; RA Birken S., Fetherston J., Canfield R.E., Boime I.; RT "The amino acid sequences of the prepeptides contained in the alpha RT and beta subunits of human choriogonadotropin."; RL J. Biol. Chem. 256:1816-1823(1981). RN [6] RP PROTEIN SEQUENCE OF 28-116. RX PubMed=890569; RA Sairam M.R., Li C.H.; RT "Human pituitary thyrotropin. The primary structure of the alpha and RT beta subunits."; RL Can. J. Biochem. 55:755-760(1977). RN [7] RP PROTEIN SEQUENCE OF 28-116. RX PubMed=5065401; DOI=10.1016/0006-291X(72)90380-4; RA Sairam M.R., Papkoff H., Li C.H.; RT "Human pituitary interstitial cell stimulating hormone: primary RT structure of the alpha-subunit."; RL Biochem. Biophys. Res. Commun. 48:530-537(1972). RN [8] RP PROTEIN SEQUENCE, AND SEQUENCE REVISION. RA Keutmann H.T., Williams R.M., Bishop W.H., Ryan R.J.; RT "Structure of human luteninizing hormone."; RL Fed. Proc. 37:1828-1828(1978). RN [9] RP PROTEIN SEQUENCE OF 25-116. RC TISSUE=Pituitary; RX PubMed=1158880; RA Rathnam P., Saxena B.B.; RT "Primary amino acid sequence of follicle-stimulating hormone from RT human pituitary glands. I. alpha subunit."; RL J. Biol. Chem. 250:6735-6746(1975). RN [10] RP PROTEIN SEQUENCE OF 28-116. RX PubMed=4835135; DOI=10.1210/jcem-39-1-199; RA Shome B., Parlow A.F.; RT "Human follicle stimulating hormone (hFSH): first proposal for the RT amino acid sequence of the alpha-subunit (hFSHa) and first RT demonstration of its identity with the alpha-subunit of human RT luteinizing hormone (hLHa)."; RL J. Clin. Endocrinol. Metab. 39:199-202(1974). RN [11] RP PROTEIN SEQUENCE OF 25-116. RX PubMed=1150658; RA Morgan F.J., Birken S., Canfield R.E.; RT "The amino acid sequence of human chorionic gonadotropin. The alpha RT subunit and beta subunit."; RL J. Biol. Chem. 250:5247-5258(1975). RN [12] RP PROTEIN SEQUENCE OF 25-116. RX PubMed=4745444; RA Bellisario R., Carlsen R.B., Bahl O.P.; RT "Human chorionic gonadotropin. Linear amino acid sequence of the alpha RT subunit."; RL J. Biol. Chem. 248:6796-6809(1973). RN [13] RP PRELIMINARY ASSIGNMENT OF DISULFIDE BONDS. RX PubMed=6774759; DOI=10.1016/0005-2795(80)90084-7; RA Fujiki Y., Rathnam P., Saxena B.B.; RT "Studies on the disulfide bonds in human pituitary follicle- RT stimulating hormone."; RL Biochim. Biophys. Acta 624:428-435(1980). RN [14] RP PRELIMINARY ASSIGNMENT OF DISULFIDE BONDS. RX PubMed=7410374; RA Mise T., Bahl O.P.; RT "Assignment of disulfide bonds in the alpha subunit of human chorionic RT gonadotropin."; RL J. Biol. Chem. 255:8516-8522(1980). RN [15] RP STRUCTURE OF CARBOHYDRATES. RX PubMed=1991473; DOI=10.1111/j.1432-1033.1991.tb15702.x; RA Weisshaar G., Hiyama J., Renwick A.G.C., Nimtz M.; RT "NMR investigations of the N-linked oligosaccharides at individual RT glycosylation sites of human lutropin."; RL Eur. J. Biochem. 195:257-268(1991). RN [16] RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=2494176; RA Keene J.L., Matzuk M.M., Otani T., Fauser B.C.J.M., Galway A.B., RA Hsueh A.J.W., Boime I.; RT "Expression of biologically active human follitropin in Chinese RT hamster ovary cells."; RL J. Biol. Chem. 264:4769-4775(1989). RN [17] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS). RX PubMed=8202136; DOI=10.1038/369455a0; RA Lapthorn A.J., Harris D.C., Littlejohn A., Lustbader J.W., RA Canfield R.E., Machin K.J., Morgan F.J., Isaacs N.W.; RT "Crystal structure of human chorionic gonadotropin."; RL Nature 369:455-461(1994). RN [18] RP STRUCTURE BY NMR. RX PubMed=8898911; DOI=10.1111/j.1432-1033.1996.0229t.x; RA de Beer T., van Zuylen C.W.E.M., Leeflang B.R., Haard K., Boelens R., RA Kaptein R., Kamerling J.P., Vliegenthart J.F.G.; RT "NMR studies of the free alpha subunit of human chorionic RT gonadotropin. Structural influences of N-glycosylation and the beta RT subunit on the conformation of the alpha subunit."; RL Eur. J. Biochem. 241:229-242(1996). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.92 ANGSTROMS) OF 25-116 IN COMPLEX WITH FSHB RP AND FSHR, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-76 AND ASN-102. RX PubMed=15662415; DOI=10.1038/nature03206; RA Fan Q.R., Hendrickson W.A.; RT "Structure of human follicle-stimulating hormone in complex with its RT receptor."; RL Nature 433:269-277(2005). RN [20] {ECO:0000244|PDB:4MQW} RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 25-116 IN COMPLEX WITH FSHB RP AND FSHR, FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BONDS, RP GLYCOSYLATION AT ASN-76 AND ASN-102, AND MUTAGENESIS OF ASN-76. RX PubMed=24692546; DOI=10.1074/jbc.M114.549592; RA Jiang X., Fischer D., Chen X., McKenna S.D., Liu H., Sriraman V., RA Yu H.N., Goutopoulos A., Arkinstall S., He X.; RT "Evidence for follicle-stimulating hormone receptor as a functional RT trimer."; RL J. Biol. Chem. 289:14273-14282(2014). CC -!- FUNCTION: Shared alpha chain of the active heterodimeric CC glycoprotein hormones thyrotropin/thyroid stimulating hormone/TSH, CC lutropin/luteinizing hormone/LH, follitropin/follicle stimulating CC hormone/FSH and choriogonadotropin/CG. These hormones bind CC specific receptors on target cells that in turn activate CC downstream signaling pathways. {ECO:0000269|PubMed:24692546, CC ECO:0000269|PubMed:2494176}. CC -!- SUBUNIT: Heterodimer. The active hormones thyrotropin, lutropin, CC follitropin and choriogonadotropin are heterodimers composed of CC CGA, a common alpha chain described here and a unique beta chain CC which confers their biological specificity to the hormones: TSHB CC for thyrotropin, LHB for lutropin, FSHB for follitropin and CC choriogonadotropin subunit beta/CGB for choriogonadotropin. CC {ECO:0000269|PubMed:15662415, ECO:0000269|PubMed:2494176}. CC -!- INTERACTION: CC P01225:FSHB; NbExp=4; IntAct=EBI-718913, EBI-1030645; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24692546, CC ECO:0000269|PubMed:2494176}. CC -!- SIMILARITY: Belongs to the glycoprotein hormones subunit alpha CC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Proteic grace - Issue CC 77 of December 2006; CC URL="https://web.expasy.org/spotlight/back_issues/077"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; J00152; AAD13690.1; -; Genomic_DNA. DR EMBL; J00150; AAD13690.1; JOINED; Genomic_DNA. DR EMBL; J00151; AAD13690.1; JOINED; Genomic_DNA. DR EMBL; S70585; AAB30827.1; -; Genomic_DNA. DR EMBL; S70583; AAB30827.1; JOINED; Genomic_DNA. DR EMBL; S70584; AAB30827.1; JOINED; Genomic_DNA. DR EMBL; BC020782; AAH20782.1; -; mRNA. DR EMBL; BC055080; AAH55080.1; -; mRNA. DR EMBL; V00518; CAA23777.1; -; mRNA. DR CCDS; CCDS5007.1; -. DR PIR; A93213; TTHUAP. DR RefSeq; NP_000726.1; NM_000735.3. DR RefSeq; NP_001239312.1; NM_001252383.1. DR UniGene; Hs.119689; -. DR PDB; 1DZ7; NMR; -; A=25-116. DR PDB; 1E9J; NMR; -; A=25-116. DR PDB; 1FL7; X-ray; 3.00 A; A/C=25-116. DR PDB; 1HCN; X-ray; 2.60 A; A=25-116. DR PDB; 1HD4; NMR; -; A=25-116. DR PDB; 1HRP; X-ray; 3.00 A; A=25-116. DR PDB; 1QFW; X-ray; 3.50 A; A=25-116. DR PDB; 1XUL; Model; -; A=25-116. DR PDB; 1XWD; X-ray; 2.92 A; A/D=25-116. DR PDB; 4AY9; X-ray; 2.50 A; A/D/G=25-116. DR PDB; 4MQW; X-ray; 2.90 A; A/D/G=25-116. DR PDBsum; 1DZ7; -. DR PDBsum; 1E9J; -. DR PDBsum; 1FL7; -. DR PDBsum; 1HCN; -. DR PDBsum; 1HD4; -. DR PDBsum; 1HRP; -. DR PDBsum; 1QFW; -. DR PDBsum; 1XUL; -. DR PDBsum; 1XWD; -. DR PDBsum; 4AY9; -. DR PDBsum; 4MQW; -. DR ProteinModelPortal; P01215; -. DR SMR; P01215; -. DR BioGrid; 107507; 6. DR DIP; DIP-6182N; -. DR IntAct; P01215; 3. DR MINT; P01215; -. DR STRING; 9606.ENSP00000358595; -. DR ChEMBL; CHEMBL2146305; -. DR GlyConnect; 165; -. DR GlyConnect; 194; -. DR GlyConnect; 88; -. DR iPTMnet; P01215; -. DR PhosphoSitePlus; P01215; -. DR UniCarbKB; P01215; -. DR BioMuta; CGA; -. DR DMDM; 121312; -. DR jPOST; P01215; -. DR PaxDb; P01215; -. DR PeptideAtlas; P01215; -. DR PRIDE; P01215; -. DR ProteomicsDB; 51346; -. DR DNASU; 1081; -. DR Ensembl; ENST00000627148; ENSP00000486024; ENSG00000135346. DR GeneID; 1081; -. DR KEGG; hsa:1081; -. DR UCSC; uc063pyi.1; human. DR CTD; 1081; -. DR DisGeNET; 1081; -. DR EuPathDB; HostDB:ENSG00000135346.8; -. DR GeneCards; CGA; -. DR HGNC; HGNC:1885; CGA. DR HPA; CAB023350; -. DR HPA; HPA029698; -. DR MIM; 118850; gene. DR neXtProt; NX_P01215; -. DR OpenTargets; ENSG00000135346; -. DR PharmGKB; PA26433; -. DR eggNOG; ENOG410IWI0; Eukaryota. DR eggNOG; ENOG4111Q75; LUCA. DR GeneTree; ENSGT00390000012242; -. DR HOGENOM; HOG000232008; -. DR HOVERGEN; HBG000452; -. DR InParanoid; P01215; -. DR KO; K08522; -. DR OrthoDB; 913381at2759; -. DR PhylomeDB; P01215; -. DR TreeFam; TF332733; -. DR Reactome; R-HSA-193048; Androgen biosynthesis. DR Reactome; R-HSA-193993; Mineralocorticoid biosynthesis. DR Reactome; R-HSA-209822; Glycoprotein hormones. DR Reactome; R-HSA-209968; Thyroxine biosynthesis. DR Reactome; R-HSA-375281; Hormone ligand-binding receptors. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR Reactome; R-HSA-8866910; TFAP2 (AP-2) family regulates transcription of growth factors and their receptors. DR Reactome; R-HSA-975578; Reactions specific to the complex N-glycan synthesis pathway. DR SABIO-RK; P01215; -. DR SIGNOR; P01215; -. DR ChiTaRS; CGA; human. DR EvolutionaryTrace; P01215; -. DR GeneWiki; Chorionic_gonadotropin_alpha; -. DR GenomeRNAi; 1081; -. DR PRO; PR:P01215; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000135346; Expressed in 91 organ(s), highest expression level in placenta. DR ExpressionAtlas; P01215; baseline and differential. DR Genevisible; P01215; HS. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0016914; C:follicle-stimulating hormone complex; IDA:UniProtKB. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0016913; F:follicle-stimulating hormone activity; IDA:UniProtKB. DR GO; GO:0005179; F:hormone activity; IMP:AgBase. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0016486; P:peptide hormone processing; TAS:Reactome. DR GO; GO:0030335; P:positive regulation of cell migration; NAS:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; NAS:BHF-UCL. DR GO; GO:0010893; P:positive regulation of steroid biosynthetic process; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; NAS:BHF-UCL. DR GO; GO:0010469; P:regulation of signaling receptor activity; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; TAS:Reactome. DR Gene3D; 2.10.90.10; -; 1. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR000476; Glyco_hormone. DR PANTHER; PTHR11509; PTHR11509; 1. DR Pfam; PF00236; Hormone_6; 1. DR PRINTS; PR00274; GLYCOHORMONE. DR SMART; SM00067; GHA; 1. DR SUPFAM; SSF57501; SSF57501; 1. DR PROSITE; PS00779; GLYCO_HORMONE_ALPHA_1; 1. DR PROSITE; PS00780; GLYCO_HORMONE_ALPHA_2; 1. DR PROSITE; PS50277; GLYCO_HORMONE_ALPHA_3; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Hormone; Reference proteome; Secreted; KW Signal. FT SIGNAL 1 24 {ECO:0000269|PubMed:1150658, FT ECO:0000269|PubMed:1158880, FT ECO:0000269|PubMed:4745444, FT ECO:0000269|PubMed:481597}. FT CHAIN 25 116 Glycoprotein hormones alpha chain. FT /FTId=PRO_0000011640. FT CARBOHYD 76 76 N-linked (GlcNAc...) asparagine. FT {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:15662415, FT ECO:0000269|PubMed:24692546}. FT /FTId=CAR_000036. FT CARBOHYD 102 102 N-linked (GlcNAc...) asparagine. FT {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:15662415, FT ECO:0000269|PubMed:24692546}. FT /FTId=CAR_000037. FT DISULFID 31 55 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:15662415, FT ECO:0000269|PubMed:24692546, FT ECO:0000269|PubMed:8202136}. FT DISULFID 34 84 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:15662415, FT ECO:0000269|PubMed:24692546, FT ECO:0000269|PubMed:8202136}. FT DISULFID 52 106 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:15662415, FT ECO:0000269|PubMed:24692546, FT ECO:0000269|PubMed:8202136}. FT DISULFID 56 108 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:15662415, FT ECO:0000269|PubMed:24692546, FT ECO:0000269|PubMed:8202136}. FT DISULFID 83 111 {ECO:0000244|PDB:4MQW, FT ECO:0000269|PubMed:15662415, FT ECO:0000269|PubMed:24692546, FT ECO:0000269|PubMed:8202136}. FT MUTAGEN 76 76 N->D: Increases from 1 to 3 the number of FT FSH binding a single FSHR receptor. FT {ECO:0000269|PubMed:24692546}. FT CONFLICT 29 29 Q -> E (in Ref. 9; AA sequence). FT {ECO:0000305}. FT CONFLICT 108 109 CS -> SC (in Ref. 6; AA sequence and 7; FT AA sequence). {ECO:0000305}. FT STRAND 33 38 {ECO:0000244|PDB:4AY9}. FT TURN 40 42 {ECO:0000244|PDB:4AY9}. FT STRAND 50 62 {ECO:0000244|PDB:4AY9}. FT HELIX 65 68 {ECO:0000244|PDB:4AY9}. FT STRAND 76 80 {ECO:0000244|PDB:4AY9}. FT STRAND 83 94 {ECO:0000244|PDB:4AY9}. FT TURN 95 97 {ECO:0000244|PDB:4AY9}. FT STRAND 98 109 {ECO:0000244|PDB:4AY9}. FT STRAND 112 114 {ECO:0000244|PDB:1DZ7}. SQ SEQUENCE 116 AA; 13075 MW; F0623CD8CC90CFCD CRC64; MDYYRKYAAI FLVTLSVFLH VLHSAPDVQD CPECTLQENP FFSQPGAPIL QCMGCCFSRA YPTPLRSKKT MLVQKNVTSE STCCVAKSYN RVTVMGGFKV ENHTACHCST CYYHKS //